Foot-and-mouth disease (FMD) is a highly contagious disease of domestic and wild cloven-hoofed animals including cattle, swine, goats and deer which rapidly replicates in the host and spreads to in-contact susceptible animals. The disease is characterized by fever, lameness, and vesicular lesions of the tongue, feet, snout, and teats resulting in high morbidity, but low mortality in adult animals. FMDV infection drives an acute vesicular disease in cattle, buffaloes, sheep, goats and pigs, which may develop into persistent infection (excluding pigs). FMDV can infect many other mammalian species, including antelopes, elephants, hedgehogs, among others. It is though that the original FMDV natural host might be the African buffalo since: i) it is persistently infected and ii) disease is rarely observed.
The causative agent of FMD is the foot-and-mouth disease virus (FMDV), a Group IV (+) ssRNA virus of the Aphthovirus genus, of the Picornaviridae family. FMDV occurs in seven major serotypes: O, A, C, SAT-1, SAT-2, SAT-3, and Asia-1. These serotypes are regionally restricted with the O serotype most common world-wide. The single-stranded, positive-sense RNA genome of FMDV is approximately 8500 bases surrounded by an icosahedral capsid with 60 copies each of four structural proteins VP1-VP4. The viral proteins are antigenically highly variable within its several subtypes including A, Asia 1, O, C, SAT1, SAT2, and SAT3.
FMD is economically devastating and infection of cloven-hoofed livestock can result in significant losses. Recent outbreaks have resulted in billions of dollars lost. Outbreaks have recently occurred in a number of previously disease free countries including Taiwan in 1997, United Kingdom and Netherlands in 2001, and the emergence in several South American countries has risen the awareness of the economically destructive virus. Furthermore, there is world-wide concern that a possible economic terrorist attack employing FMDV to target countries with large livestock industries, such as the US $100 billion/year livestock industry.
Previous measures to control FMDV include slaughter of the infected or in-contact animals and decontamination. Countries that slaughter their livestock due to a FMDV outbreak can only resume livestock activities if the countries have FMDV free status for 3 months after the last outbreak. Countries usually use vaccination of the animals to treat an FMDV outbreak as a last resort because countries that have vaccinated and do not slaughter the animals must wait an entire year to regain FMD free status. Countries, however, are looking to vaccinate their animals before any FMDV outbreak and would be able to retain their FMD free status.
In the past, FMDV vaccines included chemically inactivated whole virus antigen in conjunction with an adjuvant; however, there are disadvantages to this because it requires expensive high-containment manufacturing facilities to produce the vaccine. Over the past 25-30 years investigators have been trying to develop a vaccine that provides protection after a single inoculation. These efforts include the use of VP1 purified from virus particles, bioengineered VP1, VP1 peptides, chemically synthesized VP1 peptides, live vectors expressing VP1 epitopes, inoculation with DNA encoding VP1 epitopes, and using the full capsid protein VP1-VP4 produced from FMDV-infected cultures or delivery of the VP1-VP4 capsid via replication defective human adenovirus type 5 (Ad5) vector. All of these approaches present only a limited number of epitopes across all the subtypes of the FMDV viruses to the inoculated animal.
Accordingly, there is a need in the art for a vaccine and methods of diagnosing FMDV infected mammals that is suitable to provide protection against a plurality of epitopes of FMDV across the various subtypes of FDMV.